Surufatinib for the treatment of advanced extrapancreatic neuroendocrine tumors

ABSTRACT

Introduction: Surufatinib (also known as HMPL-012, sulfatinib) is a novel oral tyrosine kinase inhibitor (TKI), which has the dual activity of anti-angiogenesis and immune regulation. In December 2020, surufatinib was approved as a monotherapy for unresectable locally advanced or metastatic, progressive nonfunctioning, well differentiated (grade 1 or 2) extrapancreatic neuroendocrine tumors (epNETs) in China.

Areas covered: In this paper, the chemical properties, mechanism of action, pharmacokinetics, clinical efficacy, safety, and tolerability of surufatinib for treatment of advanced extrapancreatic NETs are introduced in detail. We performed a systematic review of the literature in PubMed and the following keywords were used: ‘surufatinib,’ ‘sulfatinib’ and ‘HMPL-012.’

Expert opinion: Surufatinib is a potent, selective, and small-molecule TKI that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor 1 (FGFR1) and colony stimulating factor 1 receptor (CSF1R). Surufatinib showed an acceptable safety profile and encouraging antitumor activity in patients with advanced epNETs. The most frequently observed adverse events (AEs) were hypertension and proteinuria. Surufatinib provides a new treatment option for patients with advanced epNETs. More clinical trials of surufatinib are ongoing to develop a combination of therapy strategies and new indications for malignancies.

KEYWORDS:

• Extrapancreatic neuroendocrine tumors
• surufatinib
• sulfatinib
• HMPL-012
• targeted therapy

Article highlights

• Surufatinib is a novel, oral, potent, and highly selective tyrosine kinase inhibitor.

• Mechanism of action: selectively targeting VEGFR 1-3, FGFR 1, and CSF-1R, simultaneously blocking tumor angiogenesis, and modulating cancer immunity

• Surufatinib was approved as a monotherapy by the NMPA for unresectable locally advanced or metastatic, progressive non-functioning, well differentiated (grade 1 or 2) extrapancreatic NETs.

• Recommended usage and dosage of surufatinib for advanced extrapancreatic NETs: 300 mg orally, once daily (QD). Surufatinib was taken continuously for 4 weeks for one treatment cycle. It can be taken with a low-fat meal or on an empty stomach and should be swallowed whole.

• Surufatinib is well tolerated with a manageable toxicity profile. The most frequent AEs are hypertension and proteinuria.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was financially supported by the Key Research & Development Program of Shandong Province [2018GGX109006].